Tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3′-pyrrolidine derivatives which are promising therapeutic agents for diabetic complications showing a potent aldose reductase inhibitory activity are disclosed in the literature (for example, see JP-A-5-186472; and J. Med. Chem., 1998, 41, p. 4118 to 4129). Also Ranirestat [AS-3201; (3R)-2′-(4-bromo-2-fluorobenzyl)spiro[pyrrolidin-3,4′(1′H)-pyrrolo[1,2-a]pyrazine]-1′,2,3′,5(2H′)-tetraone] selected among these derivatives has been developed clinically.
The process for preparing the compound of the formula (XI) mentioned below is described in a literature, and the literature describes that the optical resolution of the compound (wherein R4 is a protecting group of a carboxyl group) into each enantiomer is carried out by forming diastereomer salts with an optically active acid [for example, (+)-camphor acid, (1S)-(+)- or (1R)-(−)-camphor-10-sulfonic acid, L-(+)- or D-(−)-tartaric acid, L-pyroglutamilic acid, (S)-(−)- or (R)-(+)-malic acid, hydrogenphosphate (S)-(+)- or (R)-(−)-1,1′-binaphthyl-2,2′-diyl, (−) or (+)-2′-nitrotartronic acid, D-(+)-tartronic acid, (−)-dibenzoyl-L-tartaric acid, (+)-dibenzoyl-D-tartaric acid, (−)-diacetyl-L-tartaric acid, etc.] according to the conventional method, followed by isolating the two diastereomer salts and converting them into free bases thereof (see, for example, JP-A-5-186472).

However there is no specific disclosure of the diastereomer salt of the compound of the formula (XI) (wherein R4 is a protecting group of a carboxyl group) and no suggestion of a direct preparation of the compound of the formula (VI′) mentioned above using the diastereomer salt.
A literature describes that racemic compounds (Ia) and (Ib) shown below can be resolved into two enantiomers by forming diastereomer salts with an optically active amine according to the conventional method, followed by separating them into two kinds of diastereomer salts by a fractional crystallization and then decomposing these salts (see, for example, JP-A-6-192222).
wherein R1 is a protecting group of a carboxyl group and R4 is a group cleavable by hydrogenolysis or a tert-butoxycarbonyl group, with proviso that when R4 is a group cleavable by hydrogenolysis, then R1 is a group cleavable by hydrolysis.
However there is no description and no suggestion on an optical resolution of the compound of the formula (Ia) wherein R4 is a hydrogen atom.
The process for preparing Ranirestat is described in the literature as shown in the below scheme (see, for example, J. Med. Chem., 1998, 41, p. 4118 to 4129).
wherein Z is a benzyloxycarbonyl group.
However there is no description and suggestion on an optical resolution of racemic ethyl 3-amino-2,5-dioxopyrrolidine-3-carboxylate.
The process for preparing optically active 2,5-dioxo-3-(pyrrol-1-yl)pyrrolidine-3-carboxylates described in the literature requires essentially a step of removing an optically active amine used as an optical resolution agent by using an acid after an optical resolution of racemic intermediates and also requires a large number of steps as shown in the scheme below (see, for example, JP-A-6-192222 and J. Med. Chem., 1998, 41, p. 4118 to 4129).
wherein Ra is a protecting group for an amino group such as a benzylcarbonyl group and Rb is a protecting group for a carboxyl group such as an ethyl group.